Bacterial vaginosis (BV) is the leading cause of vaginal tract infection in women of reproductive age in the U.S. Evidence from epidemiological studies suggests that BV is a risk factor for serious female upper genital tract infections and preterm delivery, which is the major cause of perinatal morbidity and mortality in the developed world. The estimated cost to the U.S. of BV-related complications during pregnancy is $500 million to $1 billion, per annum. BV is a polymicrobial syndrome characterized by an alteration in the normal vaginal microflora, such that the Lactobacillus-dominated populations present in healthy individuals are replaced by Gardnerella vaginalis, anaerobes, and genital mycoplasmas. Currently, the mechanisms that cause this shift in the vaginal microflora are not well understood. Development of BV is generally preceded by decreased concentrations of lactobacilli; however, mechanisms which may account for the disappearance of the vaginal lactobacilli are not well documented. The overall goal of this study is to understand the pathogenesis of BV by describing microbial interactions that could lead to the decline in vaginal lactobacilli and pave the way for the establishment of a BV-associated microflora. Preliminary data collected with undergraduate student researchers in my laboratory show that certain strains of vaginal enterococci can produce a class of antibiotics known as bacteriocins, which inhibit the growth of vaginal lactobacilli in vitro. One objective of the proposed study is to chemically purify and characterize bacteriocins produced by vaginal enterococci. The in vivo significance of such antibacterial substances as a mechanism contributing to the decline of vaginal lactobacilli will be assessed using a chemostat to model the in vivo conditions of the vagina. In addition, chemical characterization of such bacteriocins may reveal novel antibacterial agents, with future potential for the control of microbial growth, including the treatment of infectious diseases. The involvement of undergraduate students in all aspects of this project will enhance the current strengths of our institution in engaging and mentoring students in the conduct and presentation of scientific research. [unreadable] [unreadable]